Light-Addressable Nanoclusters of Ultrasmall Iron Oxide Nanoparticles for Enhanced and Dynamic Magnetic Resonance Imaging of Arthritis

Design of novel nanoplatforms with single imaging elements for dynamic and enhanced T ₁/T ₂-weighted magnetic resonance (MR) imaging of diseases still remains significantly challenging. Here, a facile strategy to synthesize light-addressable ultrasmall Fe₃O₄ nanoparticles (NPs) that can form nanoclusters (NCs) under laser irradiation for enhanced and dynamic T ₁/T ₂-weighted MR imaging of inflammatory arthritis is reported. Citric acid-stabilized ultrasmall Fe₃O₄ NPs synthesized via a solvothermal approach are linked with both the arthritis targeting ligand folic acid (FA) and light-addressable unit diazirine (DA) via polyethylene glycol (PEG) spacer. The formed ultrasmall Fe₃O₄-PEG-(DA)-FA NPs are cytocompatible, display FA-mediated targeting specificity to arthritis-associated macrophage cells, and can form NCs upon laser irradiation to have tunable r ₁ and r ₂ relaxivities by varying the laser irradiation duration. With these properties owned, the designed Fe₃O₄-PEG-(DA)-FA NPs can be used for T ₁-weighted MR imaging of arthritis without lasers and enhanced dual-mode T ₁/T ₂-weighted MR imaging of arthritis under laser irradiation due to the formation of NCs that have extended accumulation within the arthritis region and limited intravasation back to the blood circulation. The designed light-addressable Fe₃O₄-PEG-(DA)-FA NPs may be used as a promising platform for dynamic and precision T ₁/T ₂-weighted MR imaging of other diseases.